Projects

Ageing and senescence

Ageing is a significant problem facing society today, there is currently a keen desire to promote healthy ageing, with the absence of disease. However it is known that ionizing radiation can induce premature ageing. The mechanisms behind this are not fullyunderstood, there is evidence to suggest that small extracellular vesicles can propagate the premature ageing effect. Supported by the Dunhill medical trust we are investigating how exosomes from cells that have aged normally and exosomes from prematurely aged irradiated cells affect unirradiated cells of variousages. We also want to identify the contents of exosomes that maybe responsible for any observed effect.

Cancer metastasis

A prominent treatment modality for cancer is radiotherapy. Radiotherpay is an effective tool to destroy cancer cells but despite huge technical advances, radiotherapy in some senses is still a relatively crude. There are some biological processes that are not fullyunderstood particularly in terms of signalling post radiotherapy. Within the lab we are investigating how and in what way irradiated cancer cells signal to neighbouring cells. We are also interested in what functional changes this signalling induces. It is hoped by understanding these processes we can enhancecertain aspects that we desire for treatment and limit those that are detrimental to treatment. By understanding the biology we may also be able to use certain information for tailoring treatment to certain individuals, the idea of personalised medicine.

Jumping genes and genomic instability

The human genome contains repetitive sequences called long interspersed element-1 r LINE-1. These sequences comprise approximately 17% of the genome, the majority are dormant and remain silent for the life of the organism. A fraction however has the ability to“retrotranspose”, a process where they copy and reinsert themselves somewhere within the genome. This could potentially interrupt important gene functions. The retrotransposition process is tightly controlled however it has been suggested that ionizing radiation can remove this control and permitretrotransposition. We are currently investigating this possibility as a cause of radiation induced genomic instability and the mechanisms behind it.

Radiation type, dose and dose rates and its influence on genomic instability

Radiation induced non-targeted effects (described in “About”) is influenced by dose and dose rate of radiation exposure, radiation quality as well as genetics. We are currently exploring two aspects of these influencing factors.

1. The type of radiation: Radiation can exist in a particulate form (α-particles) or as an electromagnetic wave (X-rays). The physics associated with these different types has the potential to induce different biological effects, we are exploring these different effects and establishing mechanisms behind them.

2. Dose rate: Radiation exposure can be arbitrarily divided into acute or chronic exposures. The question of biological response when two individuals receive the same dose of radiation but one is exposed over 10 minutes (acute exposure) while the other is exposed over 10 days (chronic exposure) is an important question to consider. We have been working to identify how the biological responses differ with these two types of exposure and what the consequences are.

Sub-title 5 – Radiation induced cataract

The lens of the eye has long been considered as a radiosensitive tissue, but recent research has suggested that the radiosensitivity is even greater than previously thought with respect to cataract induction. The mechanisms of radiation cataract induction are still unclear. This is an important current public health issue, for instance for medical radiation workers, many of whom will need to amend their working practices despite a clear understanding of the effects of chronic, low dose, ionising radiation exposure. We are involved in a European supported multidisciplinary project that aims to bring together experts from across Europe to answer a number of key research questions on this topic, including: how does low dose radiation cause cataracts; is there a dose rate effect, and how does genetic background influence cataract development after radiation exposure?

Concrete outcomes are anticipatedto include: definitive information regarding the shape of the dose response curve and thus the risk of radiation cataract at doses < 500 mGy, thus strengthening the evidence base for informed radiation protection; the assessment of lens effects as biomarkers of global radiosensitivity to providepotential new tools for health risk assessment as well as the education and training of a number of earlier career scientists in low dose radiation research.

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